Washington: Mechanisms associated with a particular diabetes drug can also help to protect against&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>&nbsp;suggests a study by researchers at&nbsp;<a href="https://www.aninews.in/topic/karolinska-institutet-in-sweden" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Karolinska Institutet in Sweden</a>.The results, published in Neurology, indicate that the drug's target protein can be an interesting candidate for the treatment of&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>.<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>&nbsp;is becoming increasingly common, but there are no drugs to affect the course of the disease and the development of new drugs is a slow, costly and complex process.An alternative strategy is therefore to find already approved drugs that can prove efficacious against the disease and give them a new area of application. Diabetes drugs have been put forward as possible candidates, but so far the studies that have tested diabetes drugs for&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>&nbsp;have not produced convincing results.In the present study, researchers from Karolinska Institutet used genetic methods to study this more closely. "<a href="https://www.aninews.in/topic/genetic-variants" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Genetic variants</a>&nbsp;within or nearby the genes that encode a drug's target proteins can cause physiological changes similar to the effects of the drug," says the study's first author Bowen Tang, doctoral student at the&nbsp;<a href="https://www.aninews.in/topic/department-of-medical-epidemiology-and-biostatistics" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Department of Medical Epidemiology and Biostatistics</a>, Karolinska Institutet. "We utilise such variants to test the repurposing potential of already approved drugs."The researchers began by identifying genetic variants that mimic the pharmacological effect of diabetes drugs, namely lowering blood glucose. This was done through an analysis of data from over 300,000 participants in the UK Biobank register.The analysis identified variants in two genes that together code for the target protein of a class of diabetes drug called sulphonylureas. The researchers validated these variants by showing their association with, amongst other phenomena, higher insulin release, lower type 2 diabetes risk and higher BMI, which is consistent with the drug's effects.The researchers then examined the link between the identified genetic variants and the risk for&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>. They did this by analysing data collected previously from over 24,000 people with&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>&nbsp;and 55,000 controls. They found that the genetic variants in the sulphonylurea genes were linked to a lower risk of&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>."Our results suggest that the target protein of sulphonylureas, the KATP channel, may be a therapeutic target for the treatment and prevention of&nbsp;<a href="https://www.aninews.in/topic/alzheimers-disease" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Alzheimer's disease</a>," says the study's last author Sara Hagg, docent at the&nbsp;<a href="https://www.aninews.in/topic/department-of-medical-epidemiology-and-biostatistics" rel="noopener noreferrer" target="_blank" style="color: rgb(51, 51, 51);">Department of Medical Epidemiology and Biostatistics</a>, Karolinska Institutet. "This protein is expressed in the pancreas, but also in the brain, and further studies are needed to fully understand the underlying biology."—ANI

Mechanisms associated with a particular diabetes drug can also help to protect against Alzheimer's disease suggests a study by researchers at Karolinska Institutet in Sweden.

Target protein for diabetes can help to protect against Alzheimer's disease : Study

Washington: According to a recent study, the most common form of dementia, Alzheimer's disease at present does not have a cure or effective therapy. The study suggested that due to gaps in our understanding of how progressive neurodegenerative disorder arises in the brain.Now, a Flinders University study has shown how a protein called tau, a critical factor in the development of Alzheimer's disease, turns from normal to a disease state -- and demonstrates how this discovery could deliver a therapeutic target.Published in the journal Science Advances, the team's findings provide hope for preventing the tau transformation process from happening, thereby keeping tau in a healthy state and avoiding toxic effects on brain cells."Alongside a small peptide called amyloid-beta, the tau protein is a central factor in Alzheimer's disease. Tau is necessary for the toxic effects on brain cells that then result in impaired memory function," says senior study author Dr Arne Ittner, Senior Research Fellow in Neuroscience in the Flinders Health and Medical Research Institute.In the course of Alzheimer's disease development, tau accumulates in deposits inside brain cells. During this process, tau gets heavily modified, with various deposits made up of tau carrying multiple small changes at many different positions within the tau molecule. While such changes to tau have been known to neuropathologists for decades, it remained unclear how tau arrives at this multi-modified stage. The new study has solved part of this mystery and provides a new mechanism to explain how tau gets progressively modified. The study set out to answer whether one change at one specific spot in tau would make it easier for another spot to be modified. The team focussed on the relationship between tau and protein kinases, which are enzymes that introduce changes in tau."Usually, protein kinases target specific spots, called phosphorylation sites, in tau and other proteins, and introduce changes only at these specific spots," says study lead author Dr Kristie Stefanoska, Research Fellow in Dementia at Flinders University."However, we suspected that some of these enzymes are able to target several spots in tau and would do so even more efficiently if tau were already modified at one spot to begin with."The researchers conducted a large experiment that included up to 20 different changes in tau and 12 enzymes, focussing on the most abundant type of change seen in tau from the brains of Alzheimer's patients.While the study did discover that one change in tau does makes it easier for another change to be introduced, it was also able to identify "master sites" in tau, being specific spots that govern subsequent modifications at most of the other sites."By modifying these master sites, we were able to drive modification at multiple other spots within tau, leading to a similar state seen in the brains of Alzheimer's patients," says Dr Ittner.The next step for the team was to see whether master sites could be targeted to reduce the toxic properties of tau in Alzheimer's, in a bid to improve memory function. The current study employed mice that have both amyloid and tau and developed Alzheimer's-like symptoms, including memory deficits. The researchers found that mice did not develop memory deficits when they had a version of tau that lacked one of the identified master sites, compared with mice that had the usual version of tau.The team will now investigate how its findings can be translated into a treatment."We have shown that this new concept has therapeutic potential, but future work is needed to understand the role of these master sites in health and disease," says Dr Stefanoska."Tau modification in Alzheimer's disease is a complicated process. Ours is the first study to link an initial change in tau with multi-site modification along the entire protein."The authors say the new mechanism and the master sites at its centre could apply to a range of neurological disorders in which tau is involved, including Parkinson's disease, concussion-induced chronic brain injury and stroke."Slowing down the changes at master sites of tau in these diseases may put the brakes on tau toxicity and dementia," says Dr Ittner. "This new mechanism helps us understand why there is extensive tau modification in Alzheimer's disease in the first place. This will assist researchers and clinicians in designing means for better and earlier diagnosis."&nbsp;—ANI

According to a recent study, the most common form of dementia, Alzheimer's disease at present does not have a cure or effective therapy. The study suggested that due to gaps in our understanding of how progressive neurodegenerative disorder arises in the brain.

Study Reveals Driving Forces Of Alzheimer's Disease

Washington: Alzheimer's disease affects at least one type of visual memory by deteriorating a recently found circuit that connects the image processing areas of each brain hemisphere, according to a new MIT study.
The findings of the study published in the journal Neuron by a research team based at The Picower Institute for Learning and Memory, come from experiments in mice, but provide a physiological and mechanistic basis for prior observations in human patients: the degree of diminished brain rhythm synchrony between counterpart regions in each hemisphere correlates with the clinical severity of dementia.
"We demonstrate that there is a functional circuit that can explain this phenomenon," said lead author Chinnakkaruppan Adaikkan, a former Picower Institute postdoc who is now an assistant professor in the Centre for Brain Research at the Indian Institute of Science (IISc) in Bangalore. "In a way we uncovered a fundamental biology that was not known before."
Specifically, Adaikkan's work identified neurons that connect the primary visual cortex (V1) of each hemisphere and showed that when the cells are disrupted, either by genetic alterations that model Alzheimer's disease or by direct laboratory perturbations, brain rhythm synchrony becomes reduced and mice become significantly less able to notice when a new pattern appeared on a wall in their enclosures. Such recognition of novelty, which requires visual memory of what was there the prior day, is an ability commonly disrupted in Alzheimer's.
"This study demonstrates the propagation of gamma rhythm synchrony across the brain hemispheres via the cross hemispheric connectivity," said study senior author Li-Huei Tsai, Picower Professor and director of The Picower Institute and MIT's Aging Brain Initiative. "It also demonstrates that the disruption of this circuit in AD mouse models is associated with specific behavioral deficits."
Cross-hemispheric cells
In the study, Adaikkan, Tsai, Thomas McHugh and co-authors discovered and traced V1 neurons that extended their axons all the way through the corpus callosum, which connects the brain's hemispheres, to cells in the V1 on the brain's other side. There, they found, the cross-hemispheric (CH) neurons forged connections, or synapses, with target cells, providing them with "excitatory" stimulation to drive their activity. Adaikkan also found that CH neurons were much more likely to be activated by a novelty discrimination task than V1 neurons in general or neurons in other regions heavily involved in memory such as the hippocampus or the prefrontal cortex.
Curious about how this might differ in Alzheimer's disease, the team looked at the activity of the cells in two different Alzheimer's mouse models. The found that CH cell activity was significantly lessened amid the disease. Unsurprisingly, Alzheimer's mice fared much poorer in novelty discrimination tasks.
The team examined the CH cells closely and found that they gather incoming input from a variety of other cells within their V1 and other regions in their hemisphere that process visual information. When they compared the incoming connections of healthy CH neurons to those in CH cells afflicted with Alzheimer's, they found that cells in the disease condition had significantly less infrastructure for hosting incoming connections (measured in terms of synapse-hosting spines protruding from the vine-like dendrites that sprawl out of the cell body).
Given the observations correlating reduced brain rhythm synchrony and memory performance in Alzheimer's, the team wondered if that occurred in the mice, too. To find out, they custom-designed electrodes to measure rhythmic activity simultaneously in all cortical layers of each hemisphere's V1. They observed that cross-hemispheric synchrony increased notably between the V1s when mice engaged in novelty discrimination but that the synchrony, both at high "gamma" and lower "theta" frequency rhythms, was significantly lower in the Alzheimer's mice than it was in healthy mice.
Adaikkan's evidence at that point was strong, but still only suggestive, that CH neurons provided the means by which the V1 regions on each side of the brain could coordinate to enable novelty discrimination, and that this ability became undermined by Alzheimer's degradation of the CH cells' connectivity. To more directly determine whether the CH circuit played such a causal, consequential role, the team directly intervened to disrupt them, testing what effect targeted perturbations had.
They found that chemically inhibiting CH cells disrupted rhythm synchrony between V1s, mirroring measures made in Alzheimer's model mice. Moreover, disrupting CH activity undermined novelty discrimination ability. To further test whether it was the cells' cross-hemispheric nature that mattered specifically, they engineered CH cells to be controllable with flashes of light (a technology called "optogenetics"). When they shined the light on the connections, they forged in the other hemisphere to inhibit those, they found that doing so again compromised visual discrimination ability.
All together, the study results show that CH cells in V1 connect with neurons in the counterpart area of the opposite hemisphere to synchronize neural activity needed for properly recognizing novelty, but that Alzheimer's disease damages their ability to do that job.
Adaikkan said he is curious to now look at other potential cross-hemispheric connections and how they may be affected in Alzheimer's disease, too. He said he also wants to study what happens to synchrony at other rhythm frequencies.
In addition to Adaikkan and Tsai, the study's other authors are Jun Wang, Karim Abdelall, Steven Middleton, Lorenzo Bozzelli, and Ian Wickersham. —ANI

Alzheimer's disease affects at least one type of visual memory by deteriorating a recently found circuit that connects the image processing areas of each brain hemisphere, according to a new MIT study.

Alzheimer's May Lead To Loss Of Visual Memory: Study

New York: Daily intake of green tea and an occasional glass of red wine may help reduce plaques in the brain associated with Alzheimer's disease, according to a study.
The researchers from Tufts University in the US found that two common compounds -- green tea catechins and resveratrol, found in red wine and other foods -- reduced the formation of plaques in neural cells with few or no side effects.
They tested 21 different compounds in Alzheimer's-afflicted neural cells in the lab, measuring the compounds' effect on the growth of sticky beta amyloid plaques. These plaques develop in the brains of people with Alzheimer's.
The researchers reported their findings in the journal Free Radical Biology and Medicine.
Finding a compound "that could diminish the plaques regardless of the virus component would be ideal, because that would show that regardless of the cause of Alzheimer's, you might still see some kind of improvement," said Dana Cairns, a research associate in the Kaplan Lab in the School of Engineering who led the research.
The initial screening was done in simpler models, and compounds that had a positive effect were then tested in the 3D neural tissue model.
That model is created using a non-reactive silk sponge seeded with human skin cells that, through genetic reprogramming, are converted into neural stem cell progenitors. Those cells grow and populate the sponge, "which allows for 3D network formation of neurons similar to what you'd see in the human brain", Cairns noted.
The initial screen found five compounds had "really robust prevention of these plaques", Cairns said.
In addition to the green tea compounds and resveratrol, they also found curcumin from turmeric, the diabetic medication Metformin, and a compound called citicoline prevented plaques from forming and did not have antiviral effects.
"We hoped to find compounds that would be harmless and show some level of efficacy," she said.
Green tea compounds and resveratrol met that standard.
Green tea catechins -- molecules in the tea leaves that have an antioxidant effect -- have been explored as a potential treatment for cancers, and resveratrol has been tested for anti-aging properties.
Cairns, however, cautioned that seeing effects in the lab "doesn't always necessarily translate to what you might see in a patient".
Still, the discovery is significant because there is no cure for Alzheimer's or a way to prevent its progression, aside from several potential drugs developed by pharmaceutical companies that are still in trials, the researchers noted.—IANS

Daily intake of green tea and an occasional glass of red wine may help reduce plaques in the brain associated with Alzheimer's disease, according to a study.

Green Tea, Red Wine Can Reduce Alzheimer's Plaques Sans Side Effects

Boston: The fifth most common cause of death for persons over 65 is Alzheimer's disease (AD). A relatively recent strategy tries to treat the brain, while many prospective treatments for neurodegenerative disease concentrate on creating medications to target major offenders.
A neurosurgical procedure called deep brain stimulation (DBS) uses electrical stimulation of brain circuits to treat the symptoms of conditions including Parkinson's disease and obsessive-compulsive disorder. DBS has been used experimentally in AD patients with varying degrees of success and variability in cognitive outcomes. These various results could be the result of variations in electrode placements between people.
Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, compared DBS targets in AD patients previously treated at seven international sites, finding that stimulating the intersection of two particular brain networks correlated with better patient outcomes than stimulating nearby sites. Findings are published in Nature Communications. "Not many Alzheimer's patients have been treated with DBS, and so isolating a targetable network and showing that it could be predictive of patient outcomes was exciting," said corresponding author Andreas Horn, MD, PhD, of the Center for Brain Circuit Therapeutics. "We refined an optimal DBS site, which future clinical trials of DBS may now use, going forward. If more patients are stimulated at this region, we may see clearer evidence across the group supporting the effectiveness of DBS." With the collaboration of colleagues from Toronto Western Hospital and six other centres, forty-six patients with mild AD treated with DBS to the fornix (fx-DBS) were included in this study. The fornix is an essential structure involved in memory formation. Brigham researchers developed software capable of precisely registering fx-DBS sites from individual patients into a standardized map of the brain. From there, the researchers calculated the target associated with optimal clinical outcomes and determined what modulations of local tracts and whole-brain networks led to the best results.
Cognitive improvement was associated with DBS to the direct interface between the fornix and bed nucleus of the stria terminalis (involved in emotional and behavioural responses), with tract connections to the circuit of Papez playing a role as well (this circuit connects to the hippocampus, a major centre for memory formation).
Using an approach inspired by the machine-learning literature, the researchers validated their findings in a test cohort of 18 patients, whose data had been excluded from the initial stages of the research. They developed a model that was able to accurately determine clinical outcomes in these 18 patients based on where electrodes had been placed during their fx-DBS procedures.
The authors emphasize that this was a retrospective study, and prospective validation is required to further confirm their findings. They emphasize that neurodegeneration will progress even in patients who respond well to fx-DBS, but the procedure can potentially ameliorate symptoms.
As clinical trials of DBS continue, the researchers are looking to collaborate further with centres that conduct DBS to better define targetable networks for AD. They are also interested in further studying the exact circuits involved in memory formation based on stroke lesions that lead to cognitive decline.
"The data we used in this study is unique, and it was an honour that the team entrusted us with it so that we could apply methods we have developed over the past ten years to identify the sites in the brain that matter most for DBS in AD," Horn said. "This is still basic science, but it may give hope in terms of potential treatments that, if applied correctly, could lead to symptomatic improvements." —ANI

The fifth most common cause of death for persons over 65 is Alzheimer's disease (AD). A relatively recent strategy tries to treat the brain, while many prospective treatments for neurodegenerative disease concentrate on creating medications to target major offenders.

Women Are More Likely To Get Alzheimer's Disease: Research

Pittsburgh (Pennsylvania): A team of neuroscientists led by a University of Pittsburgh School of Medicine researcher developed a blood test to detect a new marker of Alzheimer's disease neurodegeneration.
A study based on their findings was published in the journal Brain.
The biomarker, called "brain-derived tau," or BD-tau, outperforms current blood diagnostic tests used to detect Alzheimer's-related neurodegeneration clinically. It is specific to Alzheimer's disease and correlates well with Alzheimer's neurodegeneration biomarkers in the cerebrospinal fluid (CSF).
"At present, diagnosing Alzheimer's disease requires neuroimaging," said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. "Those tests are expensive and take a long time to schedule, and a lot of patients, even in the U.S., don't have access to MRI and PET scanners. Accessibility is a major issue." Currently, to diagnose Alzheimer's disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer's Association. The guidelines, called the AT(N) Framework, require detection of three distinct components of Alzheimer's pathology--the presence of amyloid plaques, tau tangles and neurodegeneration in the brain--either by imaging or by analyzing CSF samples.
Unfortunately, both approaches suffer from economical and practical limitations, dictating the need for development of convenient and reliable AT(N) biomarkers in blood samples, collection of which is minimally invasive and requires fewer resources. The development of simple tools detecting signs of Alzheimer's in the blood without compromising on quality is an important step toward improved accessibility, said Karikari.
"The most important utility of blood biomarkers is to make people's lives better and to improve clinical confidence and risk prediction in Alzheimer's disease diagnosis," Karikari said.
Current blood diagnostic methods can accurately detect abnormalities in plasma amyloid beta and the phosphorylated form of tau, hitting two of the three necessary checkmarks to confidently diagnose Alzheimer's. But the biggest hurdle in applying the AT(N) Framework to blood samples lies in the difficulty of detecting markers of neurodegeneration that are specific to the brain and aren't influenced by potentially misleading contaminants produced elsewhere in the body.
For example, blood levels of neurofilament light, a protein marker of nerve cell damage, become elevated in Alzheimer's disease, Parkinson's and other dementias, rendering it less useful when trying to differentiate Alzheimer's disease from other neurodegenerative conditions. On the other hand, detecting total tau in the blood proved to be less informative than monitoring its levels in CSF.
By applying their knowledge of molecular biology and biochemistry of tau proteins in different tissues, such as the brain, Karikari and his team, including scientists at the University of Gothenburg, Sweden, developed a technique to selectively detect BD-tau while avoiding free-floating "big tau" proteins produced by cells outside the brain.
To do that, they designed a special antibody that selectively binds to BD-tau, making it easily detectible in the blood. They validated their assay across over 600 patient samples from five independent cohorts, including those from patients whose Alzheimer's disease diagnosis was confirmed after their deaths, as well as from patients with memory deficiencies indicative of early-stage Alzheimer's.
The tests showed that levels of BD-tau detected in blood samples of Alzheimer's disease patients using the new assay matched with levels of tau in the CSF and reliably distinguished Alzheimer's from other neurodegenerative diseases. Levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue confirmed via brain autopsy analyses.
Scientists hope that monitoring blood levels of BD-tau could improve clinical trial design and facilitate screening and enrollment of patients from populations that historically haven't been included in research cohorts.
"There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background," said Karikari. "To develop better drugs, trials need to enroll people from varied backgrounds and not just those who live close to academic medical centers. A blood test is cheaper, safer and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer's and selecting participants for clinical trial and disease monitoring."
Karikari and his team are planning to conduct large-scale clinical validation of blood BD-tau in a wide range of research groups, including those that recruit participants from diverse racial and ethnic backgrounds, from memory clinics, and from the community. Additionally, these studies will include older adults with no biological evidence of Alzheimer's disease as well as those at different stages of the disease. These projects are crucial to ensure that the biomarker results are generalizable to people from all backgrounds, and will pave the way to making BD-tau commercially available for widespread clinical and prognostic use. —ANI

A team of neuroscientists led by a University of Pittsburgh School of Medicine researcher developed a blood test to detect a new marker of Alzheimer's disease neurodegeneration.

New Biomarker Test Can Identify Alzheimer's Neurodegeneration In Blood: Study

Washington: According to a preclinical study led by Weill Cornell Medicine researchers, people with dementia have protein buildup in their astrocytes, which may cause abnormal antiviral activity and memory loss. Dysfunction in cells called neurons, which transmit messages throughout the brain, has long been the prime suspect in dementia-related cognitive deficits. But a new study, published in Science Advances, suggests that abnormal immune activity in non-neuronal brain cells called astrocytes is sufficient to cause cognitive deficits in dementia. The discovery could lead to new treatments that reduce excess immune activity in astrocytes and their detrimental effects on other brain cells and cognition. "Astrocyte dysfunction alone can drive memory loss, even when neurons and other cells are otherwise healthy," said co-senior author Dr. Anna Orr, the Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Research in the Feil Family Brain and Mind Research Institute and a member of the Helen and Robert Appel Alzheimer's Disease Research Institute at Weill Cornell Medicine. "We found, in mice, that astrocytes can cause cognitive decline through their antiviral activities, which can make neurons hyperactive." While neurons have been intensively studied in dementia and other diseases, much less research has focused on astrocytes, which many scientists viewed as playing only supporting roles to neurons in brain health. "We are very interested in the roles of astrocytes in cognitive and behavioral disorders," she said. "These cells are prevalent in the brain and perform various key functions, but their involvement in neurocognitive disorders like dementia are poorly understood." When the investigators, including first author Dr. Avital Licht-Murava, a former postdoctoral associate in the Orr lab, examined tissue samples from deceased individuals who were diagnosed with either Alzheimer's disease or frontotemporal dementia, they found an accumulation of a protein called TDP-43 in astrocytes within the hippocampus, a brain region crucial for memory. To understand the effects of this protein build-up, the team conducted a series of experiments in mouse models and brain cells grown in the laboratory. Other senior investigators that contributed to the study include Dr. Robert Schwartz at Weill Cornell Medicine and Dr. Robert Froemke at New York University. In mice, the build-up of TDP-43 in astrocytes was sufficient to cause progressive memory loss but not other behavioral changes. "Astrocytes in the hippocampus seem to be more vulnerable to this pathology." she said. To understand the causes of memory loss at the molecular level, co-senior author Dr. Adam Orr, an assistant professor of research in neuroscience in the Feil Family Brain and Mind Research Institute and a member of the Appel Alzheimer's Disease Research Institute at Weill Cornell Medicine, analyzed gene expression and found high levels of antiviral gene activities, even though no virus was present in the brain. Astrocytes produced excessive amounts of immune messengers called chemokines, which can activate CXCR3 chemokine receptors typically found on infiltrating immune cells. To their surprise, the team discovered that CXCR3 receptor levels were elevated in hippocampal neurons, and that excessive CXCR3 receptor activity made neurons "hyperactive," Dr. Anna Orr said. "Blocking CXCR3 reduced neuronal firing in individual neurons and eliminating CXCR3 in mice by genetic engineering alleviated cognitive deficits caused by astrocytic TDP-43 build-up," Dr. Adam Orr said. These experiments demonstrate that impaired astrocytes can have a detrimental role in dementia, he said. Both investigators were excited by the potential clinical implications of their findings. "For effective therapeutics, we need to consider astrocytes along with neurons," Dr. Anna Orr said. Drugs that target the identified immune pathways might help improve cognitive function in people with dementia. She noted that scientists are already testing CXCR3 blockers to treat arthritis and other inflammatory conditions in clinical trials. These drugs could be tested and potentially repurposed for dementia. This study may also provide insights into how antiviral immune responses can cause cognitive dysfunction. Previous research has linked viral infections to Alzheimer's disease and to long-term neurocognitive effects such as memory loss and brain fog. Abnormal immune activity in astrocytes might contribute to these cognitive effects as well as increase individuals' susceptibility to viral infections, which could further worsen brain health and promote some cases of dementia. The team is currently studying how TDP-43 alters antiviral activities in astrocytes and whether these changes increase brain susceptibility to viral pathogens. "Astrocytes can promote resilience or vulnerability to brain disease," Dr. Anna Orr said. "Understanding how they enable cognitive function or cause cognitive decline will be critical to understanding brain health and developing effective therapies." —ANI

According to a preclinical study led by Weill Cornell Medicine researchers, people with dementia have protein buildup in their astrocytes

Astrocyte Dysfunction Causes Cognitive Decline: Study

New York: The 100-year-old tuberculosis vaccine Bacillus Calmette-Guerin (BCG) vaccine may likely reduce risk of Alzheimer's disease and related dementias, suggests a study.  The BCG vaccine offers multiple beneficial effects, and it's currently a recommended therapy for non-muscle-invasive bladder cancer.           The findings, published in JAMA Network Open, revealed that treatment with the BCG vaccine was associated with a 20 per cent lower risk of Alzheimer's disease and related dementias.  The protective association was greater in patients aged 70 years or older, and also reduced risk of death.  Researchers from the Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH), followed 6,467 individuals for up to 15 years after they were diagnosed with non-muscle-invasive bladder cancer.  The group included 3,388 patients who underwent BCG vaccine treatment and 3,079 who served as controls, matched by factors such as age, sex, and medical comorbidities.  During follow-up, 202 patients in the BCG vaccine group and 262 in the control group developed Alzheimer's disease and related dementias.  The incidence was 8.8 per 1,000 person-years and 12.1 per 1,000 person-years in the respective groups.  In addition, 751 patients in the BCG vaccine group died while 973 people died in the control group. Thus, treatment with BCG vaccine was also associated with a 25 per cent lower risk of death.  "A vaccine like BCG, if proven effective, is a perfect example of a cost-effective, population-healtha"based solution to a devastating illness like Alzheimer's disease," Marc Weinberg, an Instructor in Psychiatry at MGH.  "We are shifting our focus towards studying the potential benefits of BCG vaccination of older adults in Alzheimer's disease-related clinical trials," he added.  If a causal link is found, it will be important to understand the mechanisms involved. Weinberg and his colleagues note that the BCG vaccine's effects on the immune system may play a role.  —IANS

The 100-year-old tuberculosis vaccine Bacillus Calmette-Guerin (BCG) vaccine may likely reduce risk of Alzheimer's disease and related dementias

Study suggests TB vax may reduce risk of Alzheimer’s

Minneapolis: People with a genetic predisposition for Alzheimer's disease may have an increased risk of epilepsy and people with a certain type of epilepsy may have an increased risk of developing Alzheimer's disease, according to a study. The findings of the study were published in the online issue of Neurology, the medical journal of the American Academy of Neurology. "Our research found that not only are people with Alzheimer's disease more likely to develop epilepsy, but also that those with focal epilepsy, which accounts for more than half of all cases of epilepsy, were more likely to develop Alzheimer's disease," said study author Jiali Pu, PhD, of Zhejiang University School of Medicine in Hangzhou, China. Researchers used a genome-wide association analysis to examine gene variation across the human genomes of 111,326 people with Alzheimer's disease and 677,663 persons without the illness. Long sections of DNA are examined in such research to find tiny changes in the genetic sequence between persons with and without Alzheimer's disease. Researchers used a study design called Mendelian randomization to determine if there was cause and effect between the genetic variations and the risk of epilepsy.  Researchers found having Alzheimer's was linked to a 5.3% increased risk of generalized epilepsy, which involves seizures that occur from both halves of the brain. Researchers also found a 1.3 per cent increased risk of focal epilepsy with hippocampal sclerosis. Focal epilepsy involves recurring seizures that affect one half of the brain. Researchers then looked at the genes of 15,212 people with epilepsy, matched to the genes of 29,677 people without epilepsy. People who had focal epilepsy with hippocampal sclerosis had nearly four times the risk of developing Alzheimer's disease compared to people without epilepsy. Researchers also analyzed the genes of 13,116 people who had data on the levels of a biomarker for Alzheimer's disease called amyloid in their cerebrospinal fluid. Lower amounts of the biomarker indicate an increased deposition of amyloid plaques in the brain. The researchers found that genes that predicted a lower amount of the biomarker were linked to an increased risk of generalized epilepsy. "More effort should be made to screen for seizures in people with Alzheimer's disease and to understand the impact of seizures on those facing these two challenging neurologic conditions," Pu added. A limitation of the study was that participants were of European ancestry, so the results may not be generalizable to people living in other countries and of different ethnicities. (ANI)

People with a genetic predisposition for Alzheimer's disease may have an increased risk of epilepsy and people with a certain type

Having Alzheimer's genes may increase risk of epilepsy: Study

New York: Regular walks can strengthen connections in and between brain networks, according to new research, adding to growing evidence linking exercise with slowing the onset of Alzheimer's disease.  Published in the Journal for Alzheimer's Disease Reports, the study examined the brains and story recollection abilities of older adults with normal brain function and those diagnosed with mild cognitive impairment, which is a slight decline in mental abilities like memory, reasoning and judgement and a risk factor for Alzheimer's.  "Historically, the brain networks we studied in this research show deterioration over time in people with mild cognitive impairment and Alzheimer's disease," said principal investigator J. Carson Smith, a kinesiology professor at University of Maryland School of Public Health.  "They become disconnected, and as a result, people lose their ability to think clearly and remember things. We're demonstrating that exercise training strengthens these connections," Smith said.  The study builds upon Smith's previous research, which showed how walking may decrease cerebral blood flow and improve brain function in older adults with mild cognitive impairment.  Thirty-three participants, who ranged between 71 and 85 years old, walked while supervised on a treadmill four days a week for 12 weeks.  Before and after this exercise regimen, researchers asked participants to read a short story and then repeat it out loud with as many details as possible.  Participants also underwent functional magnetic resonance imaging (fMRI) so researchers could measure changes in communication within and between brain networks that control cognitive function.  After 12 weeks of exercise, researchers repeated the tests and saw significant improvements in participants' story recall abilities.  "The brain activity was stronger and more synchronised, demonstrating exercise actually can induce the brain's ability to change and adapt," Smith said.  "These results provide even more hope that exercise may be useful as a way to prevent or help stabilise people with mild cognitive impairment and maybe, over the long term, delay their conversion to Alzheimer's dementia." —IANS

 Regular walks can strengthen connections in and between brain networks, according to new research, adding to growing evidence 

Walking may help improve brain connectivity, memory in elderly

Pittsburgh (US): Why do some people get Alzheimer's while others don't? Even more perplexing, why do many people with toxic amyloid aggregates in their brains--a clear marker of Alzheimer's brain pathology--never get Alzheimer's-related dementias? University of Pittsburgh School of Medicine researchers appear to have found the answer. Star-shaped brain cells called astrocytes are key to swaying the pendulum in Alzheimer's disease progression, shows new game-changing research published today in Nature Medicine. By testing the blood of more than 1,000 cognitively unimpaired elderly people with and without amyloid pathology, the Pitt-led research team found that only those who had a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would progress to symptomatic Alzheimer's in the future, a critical discovery for drug development aimed at halting progression. "Our study argues that testing for the presence of brain amyloid along with blood biomarkers of astrocyte reactivity is the optimal screening to identify patients who are most at risk for progressing to Alzheimer's disease," said senior author Tharick Pascoal, M.D., Ph.D., associate professor of psychiatry and neurology at Pitt. "This puts astrocytes at the center as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer's disease." Alzheimer's disease is a neurodegenerative condition that causes progressive memory loss and dementia, robbing patients of many productive years of life. At the tissue level, the hallmark of Alzheimer's disease is an accumulation of amyloid plaques--protein aggregates lodged between nerve cells of the brain--and clumps of disordered protein fibers, called tau tangles, forming inside the neurons. For many decades brain scientists believed that an accumulation of amyloid plaques and tau tangles is not only a sign of Alzheimer's disease but also its direct culprit. This assumption also led drug manufacturers to heavily invest into molecules targeting amyloid and tau, overlooking the contribution of other brain processes, such as the neuroimmune system. Recent discoveries by groups like Pascoal's suggest that the disruption of other brain processes, such as heightened brain inflammation, might be just as important as amyloid burden itself in starting the pathological cascade of neuronal death that causes rapid cognitive decline. In his previous research, Pascoal and his group found that brain tissue inflammation triggers the spread of pathologically misfolded proteins in the brain and is a direct cause of eventual cognitive impairment in patients with Alzheimer's disease. Now, almost two years later, researchers revealed that the cognitive impairment can be predicted by a blood test. Astrocytes are specialized cells abundant in the brain tissue. Just as other members of the glia--resident immune cells of the brain--astrocytes support neuronal cells by supplying them with nutrients and oxygen and protecting them from pathogens. But because glial cells don't conduct electricity and, at first, didn't seem to play a direct role in how neurons communicate with one another, their role in health and disease had been overlooked. The latest research from Pitt changes that. "Astrocytes coordinate brain amyloid and tau relationship like a conductor directing the orchestra," said lead author of the study Bruna Bellaver, Ph.D., postdoctoral associate at Pitt. "This can be a game-changer to the field, since glial biomarkers in general are not considered in any main disease model." Scientists tested blood samples from participants in three independent studies of cognitively unimpaired elderly people for biomarkers of astrocyte reactivity--glial fibrillary acidic protein, or GFAP--along with the presence of pathological tau. The study showed that only those who were positive for both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology, indicating predisposition to clinical symptoms of Alzheimer's disease. The findings have direct implications for future clinical trials for Alzheimer's drug candidates. In aiming to halt disease progression sooner, trials are moving to earlier and earlier stages of pre-symptomatic disease, making correct early diagnosis of Alzheimer's risk critical for success. Because a significant percentage of amyloid-positive individuals will not progress to clinical forms of Alzheimer's, amyloid positivity alone is not enough to determine an individual's eligibility for a therapy. Inclusion of astrocyte reactivity markers, such as GFAP, in the panel of diagnostic tests will allow for improved selection of patients who are likely to progress to later stages of Alzheimer's and, therefore, help fine-tune selection of candidates for therapeutic interventions who are more likely to benefit. Other authors of the study are Guilherme Povala, Ph.D., Pamela Ferreira, Ph.D., Joao Pedro Ferrari-Souza, Douglas Leffa, M.D., Ph.D., Firoza Lussier, M.S., Oscar Lopez, M.D., Dana Tudorascu, Ph.D., Victor Villemagne, M.D., Milos Ikonomovic, M.D., Howard Aizenstein, M.D., Ph.D., William Klunk, M.D., Ph.D., Beth Snitz, Ph.D., Rebecca Thurston, Ph.D., Ann Cohen, Ph.D., Mary Ganguli, M.D., and Thomas Karikari, Ph.D., all of Pitt; Andrea Benedet, Ph.D., Nicholas Ashton, Ph.D., Henrik Zetterberg, M.D., Ph.D., and Kaj Blennow, M.D., Ph.D., all of the University of Gothenburg, Sweden; Gallen Triana-Baltzer, Ph.D., and Hartmuth Kolb, Ph.D., both of Janssen Research and Development, La Jolla, CA; Cecile Tissot, Ph.D., Joseph Therriault, Ph.D., Stijn Servaes, Ph.D., Jenna Stevenson, Ph.D., Nesrine Rahmouni, Serge Gauthier, M.D., and Pedro Rosa-Neto, M.D., Ph.D., all of McGill University, Canada; Eduardo Zimmer, Ph.D., of the Universidade Federal do Rio Grande do Sul, Brazil; and Pauline Maki, Ph.D., of the University of Illinois, Chicago. —ANI

Why do some people get Alzheimer's while others don't? Even more perplexing

New Blood Biomarker Can Predict If Cognitively Healthy Elderly Will Develop Alzheimer's Disease: Study

Washington: Researchers at Washington University School of Medicine in St. Louis found that individuals with early-stage Alzheimer's disease when brain changes have started but before cognitive symptoms are noticeable, have a variety of gut bacteria that is distinct from the gut bacteria of healthy individuals. The research, which was published on June 14 in Science Translational Medicine, paves the way for the development of microbiome-altering preventive treatments for cognitive decline as well as the possibility of using gut bacteria to identify those who are more likely to develop dementia. "We don't yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case," said co-corresponding author Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine. "It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer's disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease." The idea of studying the connection between the gut microbiome and Alzheimer's disease came together at a youth soccer game, where Dantas and Beau M. Ances, MD, PhD, the Daniel J. Brennan Professor of Neurology, chatted while their children played. Ances treats and studies people with Alzheimer's disease; Dantas is an expert on the gut microbiome. Scientists already knew that the gut microbiomes of people with symptomatic Alzheimer's differ from the microbiomes of healthy people of the same age. But, Ances told Dantas, nobody had yet looked at the gut microbiomes of people in the critical pre-symptomatic phase. "By the time people have cognitive symptoms, there are significant changes that are often irreversible," said Ances, the other co-corresponding author. "But if you can diagnosis someone very early in the disease process, that would be the optimal time to effectively intervene with a therapy." During the early stage of Alzheimer's disease, which can last two decades or more, affected people accumulate clumps of the proteins amyloid beta and tau in their brains, but do not exhibit signs of neurodegeneration or cognitive decline. Dantas, Ances and first author Aura L. Ferreiro, PhD, then a graduate student in Dantas' lab and now a postdoctoral researcher, evaluated participants who volunteer for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University. All participants were cognitively normal. As part of this study, participants provided stool, blood and cerebrospinal fluid samples; kept food diaries; and underwent PET and MRI brain scans. To distinguish participants already in the early stage of Alzheimer's disease from those who were healthy, the researchers looked for signs of amyloid beta and tau accumulation through brain scans and cerebrospinal fluid. Of the 164 participants, about a third (49) had signs of early Alzheimer's. An analysis revealed that healthy people and people with preclinical Alzheimer's disease have markedly different gut bacteria -- in terms of the species of bacteria present and the biological processes in which those bacteria are involved -- despite eating basically the same diet. These differences correlated with amyloid and tau levels, which rise before cognitive symptoms appear, but did not correlate with neurodegeneration, which becomes evident about the time cognitive skills start to decline. These differences potentially could be used to screen for early Alzheimer's disease, the researchers said. "The nice thing about using the gut microbiome as a screening tool is its simplicity and ease," Ances said. "One day individuals may be able to provide a stool sample and find out if they are at increased risk for developing Alzheimer's disease. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps." The researchers have launched a five-year follow-up study designed to figure out whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early Alzheimer's disease. "If there is a causative link, most likely the link would be inflammatory," said Dantas, who is also a professor of pathology &amp; immunology, of biomedical engineering, of molecular microbiology and of pediatrics. "Bacteria are these amazing chemical factories, and some of their metabolites affect inflammation in the gut or even get into the bloodstream, where they can influence the immune system all over the body. All of this is speculative at this point, but if it turns out that there is a causal link, we can start thinking about whether promoting 'good' bacteria or getting rid of 'bad' bacteria could slow down or even stop the development of symptomatic Alzheimer's disease." —ANI

Researchers at Washington University School of Medicine in St. Louis found that individuals with early-stage Alzheimer's disease

Researchers Find Altered Gut Bacteria Might Be Early Sign Of Alzheimer's Disease

London: On Monday, encouraging preliminary results from a trial of the Alzheimer's medicine Donanemab were welcomed by a UK-based charity due to the treatment's apparent ability to slow down brain degeneration.
The Alzheimer's Association International Conference in Amsterdam saw the release of the study's full results by Eli Lilly, the drug's manufacturer; the results confirmed that Donanemab slowed clinical decline by 35% in people with early Alzheimer's whose brain scans showed low or medium levels of a protein called Tau, according to Alzheimer's Research UK.
People who already had an abundance of Tau showed no adverse effects. Dr. Susan Kohlhaas, Executive Director of Research &amp; Partnerships at Alzheimer's Research UK, called the findings "another milestone" that proved "the outlook for dementia and its impact on people and society is finally changing."—Inputs from Agencies

On Monday, encouraging preliminary results from a trial of the Alzheimer's medicine Donanemab were welcomed by a UK-based charity due to the treatment's apparent ability to slow down brain degeneration.

UK charity hails Alzheimer’s drug Donanemab milestone

New York: An animal study has shown that it is possible to correct the body's biological clock in Alzheimer's patients with time-restricted diets, a type of intermittent fasting focused on limiting the daily eating window without limiting the amount of food consumed.  Nearly 80 per cent of people with Alzheimer's experience difficulty sleeping and worsening cognitive function at night, confusion in the evenings, and difficulty falling and staying asleep.  A new study from researchers at University of California (UC) San Diego School of Medicine has shown in mice that it is possible to correct the circadian disruptions seen in Alzheimer's disease.  In the study, published in Cell Metabolism, mice that were fed on a time-restricted schedule showed improvements in memory and reduced accumulation of amyloid proteins in the brain. The authors say the findings will likely result in a human clinical trial.  "For many years, we assumed that the circadian disruptions seen in people with Alzheimer’s are a result of neuro-degeneration, but we’re now learning it may be the other way around -- circadian disruption may be one of the main drivers of Alzheimer’s pathology,” said senior study author Paula Desplats, a professor in the Department of Neurosciences at UC San Diego School of Medicine.  “Our findings provide the proof-of-concept for an easy and accessible way to correct these disruptions,” she added.  The researchers tested this strategy in a mouse model of Alzheimer’s disease, feeding the mice on a time-restricted schedule where they were only allowed to eat within a six-hour window each day. For humans, this would translate to about 14 hours of fasting each day.  Compared to control mice who were provided food at all hours, mice fed on the time-restricted schedule had better memory, were less hyperactive at night, followed a more regular sleep schedule and experienced fewer disruptions during sleep.  The test mice also performed better on cognitive assessments than control mice, demonstrating that the time-restricted feeding schedule was able to help mitigate the behavioural symptoms of Alzheimer’s disease.  "Anything we can do to help patients restore their circadian rhythm will make a huge difference in how we manage Alzheimer’s in the clinic and how caregivers help patients manage the disease at home,” said Desplats.  The researchers also observed improvements in the mice on a molecular level. In mice fed on a restricted schedule, the researchers found that multiple genes associated with Alzheimer’s and neuroinflammation were expressed differently.  They also found that the feeding schedule helped reduce the amount of amyloid protein that accumulated in the brain. Amyloid deposits are one of the most well-known features of Alzheimer’s disease.  “Time-restricted feeding is a strategy that people can easily and immediately integrate into their lives,” said Desplats. —IANS

An animal study has shown that it is possible to correct the body's biological clock in Alzheimer's patients 

Intermittent fasting may help Alzheimer patients improve memory, sleep

Madrid (Spain): In elderly people, cardiovascular disease and dementia frequently coexist. Nonetheless, few long-term studies have been conducted to investigate how atherosclerosis and its related risk factors affect brain health beginning in middle age. A new study by scientists at Madrid's Centro Nacional de Investigaciones Cardiovasculares (CNIC) provides new data on this relationship; the findings confirm the importance of controlling traditional cardiovascular risks factors, such as hypertension, cholesterol, diabetes, smoking, and sedentary lifestyle, not only to preserve cardiovascular health, but also to prevent Alzheimer's disease and other dementias.  The CNIC study, published in The Lancet Healthy Longevity, demonstrates that in addition to being the leading cause of cardiovascular disease, atherosclerosis and its associated risk factors are also implicated in the cerebral alterations seen in Alzheimer's disease, the most common cause of dementia. According to CNIC General Director Dr Valentín Fuster, an author on the study, the new findings are important because they open up the possibility of treating a modifiable disorder (cardiovascular disease) to prevent the development of a disease for which there is currently no curative treatment (dementia). “The sooner we act to control cardiovascular risk factors, the better it is for our brain health,” said Dr. Fuster. “Everybody knows that a healthy lifestyle and controlling cardiovascular risk factors are important for preventing a heart attack,” continued Dr Fuster. “Nevertheless, the additional information linking the same risk factors to a decline in brain health could further increase awareness of the need to acquire healthy habits from the earliest life stages.” In 2021, CNIC scientists discovered that the presence of cardiovascular risk factors and subclinical (presymptomatic) atherosclerosis in the carotid arteries (the arteries that supply the brain) was associated with lower glucose metabolism in the brains of apparently healthy 50-year-old participants in the PESA-CNIC-Santander study (Cortés-Canteli &amp; Gispert et al. JACC. 2021). Glucose metabolism in the brain is considered an indicator of brain health. The PESA-CNIC-Santander study, directed by Dr. Fuster, is a prospective study that includes more than 4000 asymptomatic middle-aged participants who have been exhaustively assessed for the presence and progression of subclinical atherosclerosis since 2010. Dr. Fuster’s team, led by Drs. Marta Cortés Canteli and Juan Domingo Gispert, have continued to monitor the cerebral health of these participants over 5 years. Their research shows that individuals who maintained a high cardiovascular risk throughout this period had a more pronounced reduction in cerebral glucose metabolism, detected using imaging techniques such as positron emission tomography (PET). “In participants with a sustained high cardiovascular risk, the decline in cerebral metabolism was three times greater than in participants who maintained a low cardiovascular risk,” commented Catarina Tristão-Pereira, first author on the study and INPhINIT fellow. Glucose is the main energy source for neurons and other brain cells. “If there is a sustained decline in cerebral glucose consumption over several years, this may limit the brain ability to withstand neurodegenerative or cerebrovascular diseases in the future,” explained Dr. Gispert, an expert in neuroimaging at the CNIC and Barcelonaßeta Research Center. Through a collaboration with Drs Henrik Zetterberg and Kaj Blennow, world experts in the identification of new blood biomarkers at the University of Gothenburg in Sweden, the CNIC team discovered that the individuals showing this metabolic decline already show signs of neuronal injury. “This is a particularly important finding because neuronal death is irreversible”, said Dr. Cortés Canteli, a neuroscientist at the CNIC and a Miguel Servet fellow at the Fundación Jiménez Díaz Health Research Institute. The CNIC team also discovered that the progression of subclinical atherosclerosis in the carotid arteries over 5 years is linked to a metabolic decline in brain regions vulnerable to Alzheimer’s disease, in addition to the effect of cardiovascular risk factors. “These results provide yet another demonstration that the detection of subclinical atherosclerosis with imaging techniques provides highly relevant information,” said Dr. Fuster, who is the principal investigator on the PESA study. “The interaction between the brain and the heart is a fascinating topic, and with this study we have seen that this relationship begins much earlier than was thought.” The scientists conclude that in light of these results, “carotid screening has great potential to identify individuals at risk of cerebral alterations and cognitive decline in the future.” In the published article they write, “this work could have important implications for clinical practice since it supports the implementation of primary cardiovascular prevention strategies early in life as a valuable approach for a healthy cerebral longevity.” “Although we still don’t know what impact this decline in cerebral metabolism has on cognitive function, the detection of neuronal injury in these individuals shows that the earlier we start to control cardiovascular risk factors, the better it will be for our brain,” concluded Dr. Cortés Canteli. —ANI

In elderly people, cardiovascular disease and dementia frequently coexist. Nonetheless

Importance Of Controlling Traditional Cardiovascular Risk Factors To Prevent Alzheimer’s Disease: Study 

Washington: Alzheimer's disease, a neurological disorder characterised with progressive cognitive decline, including memory loss, affects up to 5.8 million Americans today. Protein aggregates, made up of beta-amyloid or other proteins, occur in the brains of Alzheimer's patients. These beta-amyloid plaques appear to be a major cause of the disease. Scientists at St. Jude Children's Research Hospital discovered a subpopulation of immune cells that appear to inhibit the creation of beta-amyloid plaques, as well as the critical proteins involved in the process. The findings of the study were published today in Nature Immunology. “People typically think of the immune system as being involved in defense from bacterial or viral infection, though there is growing interest in the role of the immune system in neurodegenerative diseases,” said co-first author Jordy Saravia, Ph.D., St. Jude Department of Immunology. “We uncovered an important immune cell communication axis that is protective in an Alzheimer’s disease model.” Microglia are immunological cells in the brain that are responsible for the removal of beta-amyloid plaques. Microglia may lose their ability to clear these plaques as Alzheimer's disease progresses, instead producing inflammatory mediators that may increase beta-amyloid plaque formation. The St. Jude researchers discovered that increasing another type of immune cell called CD8+ T cells is critical for slowing this process by interacting with microglia. In turn, this connection proved critical for limiting beta-amyloid accumulation and preserving cognitive capacities in a mouse model of the disease. “Our paper is the first to demonstrate that a subpopulation of CD8+ T cells can be protective in a mouse model of Alzheimer’s disease,” said co-first author Wei Su, Ph.D., St. Jude Department of Immunology. “Moving forward, we may be able to extend this work to find an effective intervention for neurodegenerative diseases.” Previous research has established complex roles for T cells and other immune system cells in Alzheimer’s disease. In particular, research groups using other experimental systems have suggested that certain T cells with inflammatory functions worsen the disease. However, the St. Jude scientists showed that CD8+ T cells with suppressive features accumulate in the brains of both mouse models and patients with Alzheimer’s disease, highlighting that T cells play a complex role in this disease.  “We showed that CD8+ T cells can play a protective role against Alzheimer’s disease pathogenesis, although there is also evidence for a contributing role,” said corresponding author Hongbo Chi, Ph.D., St. Jude Department of Immunology. “Our results demonstrate the need to better understand these complex neuro-immune interactions to improve outcomes for this neurodegenerative disease.” To understand how T cells were delaying symptom progression in their Alzheimer’s disease model, the St. Jude group searched for the most abundant molecular interaction between CD8+ T cells and the microglia. They found a protein on the surface of CD8+ T cells, CXCR6, interacts with the protein CXCL16 expressed by microglia.  The two surface proteins, CXCR6 and CXCL16, essentially performed a handshake between the two cells, communicating in both directions. Just like the firmness of a human handshake can convey information, so can the interaction of these two proteins on the outside of their respective cells. “We found CD8+ T cells use CXCR6 to interact with CXCL16 from microglia,” Chi said. “Moreover, CD8+ T-cell accumulation, localization and function in the brain are regulated by CXCR6.”  The scientists determined how the handshake occurs and delays the onset of Alzheimer’s disease-related pathologies. The CD8+ T cells first move next to the microglia, which are localized next to the beta-amyloid plaques. Then, the CD8+ T cells use the handshake to signal to the microglia to stop causing uncontrolled inflammation, which, in turn, slows plaque growth and symptoms in the mouse models. When the scientists deleted the gene for the CD8+ T cell’s protein CXCR6, the mice developed worse Alzheimer’s disease-related symptoms. This effect was partially because the CD8+ T cells without CXCR6 failed to accumulate in the brain near the microglia or plaque site. These cells also did not acquire the appropriate suppressive function. Thus, disrupting the CD8+ T cell’s ability to perform the handshake prevented its protective effect against Alzheimer’s disease symptoms. “We have two major findings,” Chi said. “One is the crucial role of CD8+ T cells in maintaining homeostasis of the brain, thereby providing a protective role in Alzheimer’s disease.” Homeostasis is the process of keeping a system in a relatively stable state. In this case, the CD8+ T cells attempt to limit the disruption caused by microglia dysfunction and Alzheimer’s disease-related plaques. “The other major finding is identifying the central importance of the T cell protein CXCR6 for CD8+ T-cell accumulation and function in the brain,” Chi continued. “We really need to characterize these kinds of neuro-immune interactions better. Only by understanding this basic biology can we advance the field and find new treatments.” —ANI

Alzheimer's disease, a neurological disorder characterised with progressive cognitive decline, including memory loss, affects up to 5.8 million Americans today

Researchers Discover How Specialized T Cells In Brain Slow Progression Of Alzheimer’s Disease

Washington: Lack of sleep not only makes you feel horrible, but study has proven that it harms your brain as well. Long-term sleep deprivation can significantly raise the chance of developing neurological illnesses like Alzheimer's.  Researchers are trying to figure out how lack of sleep results in this damage. In a recent study published in the Journal of Proteome Research of the American Chemical Society, a team using mice discovered a protective protein whose level decreases with sleep deprivation and results in neuronal death.  Studies indicate that lack of sleep leads to neurological damage in the hippocampus, a part of the brain involved in learning and memory. To better understand the changes responsible for this effect, scientists have begun examining shifts in the abundance of proteins and RNA, which contains genetically encoded instructions derived from DNA. In this way, previous studies have identified some factors linking sleep loss to damage; however, researchers haven’t generally confirmed they play a role in cognitive function within larger animal populations. So, Fuyi Xu, Jia Mi and their colleagues set out to further explore how sleep loss damages the brain and to corroborate their findings.  To start off, the researchers evaluated how well mice navigated a simple maze and learned to recognize new objects after having been sleep-deprived for two days. They then extracted the proteins in the animals’ hippocampi and identified those whose abundance changed. Then, to further narrow the possibilities, they looked at data linking these proteins to maze performance in related strains of mice that had not experienced sleep deprivation. This approach led the researchers to pleiotrophin (PTN), which declined in the sleep-deprived mice. Through an analysis of RNA, the team identified the molecular pathway by which a loss of PTN causes cells in the hippocampus to die. When they looked at genetic studies in humans, they found that PTN is implicated in Alzheimer’s and other neurodegenerative diseases. This research has uncovered a new mechanism by which sleep protects brain function, according to the researchers, who also note that PTN levels could serve as an indicator of cognitive impairment resulting from insomnia. —ANI

Lack of sleep not only makes you feel horrible, but study has proven that it harms your brain as well. Long-term sleep deprivation

How Lack Of Sleep Can Harm Brain, Finds Study

New Delhi (The Hawk): Scientists have found that highly abundant naturally occurring plant-based polyphenols (PPs) like tannic acid found in twigs of trees like Chestnut and Oak can modulate the ferroptosis-AD axis to yield a safe, cost-effective strategy for combating Alzheimer’s disease (AD) and reduce the societal burden of this debilitating neurodegenerative disorder. AD is a widely prevalent progressive neurodegenerative disorder marked by memory and cognitive decline, yet it remains poorly understood despite decades of dedicated research. As a consequence of this, there is no therapeutics to completely cure the disease. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a significant contributor to the development of AD. Several hallmarks of AD, such as abnormal iron build up, lipid peroxidation, reactive oxygen species (ROS), and reduced activity of the antioxidant enzyme glutathione peroxidase 4 (GPX4), align with the characteristics of ferroptosis. GPX4, the master regulator of ferroptosis reduces toxic lipid peroxides formed by the iron-catalysed reaction of polyunsaturated fatty acids (PUFAs) with ROS to lipid alcohol and as such, acts as a first line of defence against ferroptosis. This is called the GPX4 pathway. While conventional approaches to combat ferroptosis have primarily focused on chelating iron and neutralizing ROS, the potential therapeutic strategies that target GPX4 pathway to alleviate ferroptosis in AD have remained unexplored. GPX4 protein synthesis in itself is an energetically demanding, low efficiency process, and therefore, molecules that can activate and elevate GPX4 levels might be the key to prevent oxidative stress implicated in chronic disorders. Study by scientists of Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), an autonomous institute of the Department of Science and Technology (DST) presents naturally occurring polyphenols (PPs) as innovative and multimodal therapeutic agent with dual capabilities to ameliorate ferroptosis and AD. The underlying mechanisms involve the inhibition of aggregation of amyloid (abnormal fibrous, proteinaceous deposits found in organs and tissues) and tau protein (abundantly found in the neurons of the central nervous system), diminishing oxidative stress, rescuing mitochondrial function, and inhibiting ferroptosis. Their study has demonstrated that the natural polyphenol, tannic acid (TA) could act as both an activator and enhancer of GPX4. This novel approach provides a conceptually advanced and comprehensive strategy for combating AD by modulating the GPX4-ferroptosis-AD axis. The ability of TA to elevate GPX4 levels even in the presence of AD pathological conditions offers exciting new avenues for targeting novel pathways in the aetiology of AD while holding promise for tackling the intricate interplay between ferroptosis and AD. The study published in the journal Chemical Sciences which steers research toward ferroptosis inhibitors presents a new dimension for drug development. This discovery may inspire medicinal chemists to explore new and derivatives of natural compounds to enhance therapeutic efficacy against AD. With a rationale of targeting both AD and ferroptosis concurrently, the team screened a library of natural polyphenols for their Fe-chelation and antioxidant abilities and singled out tannic acid as a multifunctional molecule exhibiting excellent potencies in all aspects, already establishing it as a potent candidate for mitigating several pathways of AD and ferroptosis. The discovery of TA as a ferroptosis inhibitor acting via both activation and enhancement of GPX4 presents an innovative and holistic strategy against AD. This has also established a mechanistic link between AD and ferroptosis, which had so far remained elusive. The discovery of a natural polyphenol, TA as a GPX4 activator that ameliorates Aß induced ferroptosis holds great significance and this study presents new opportunities for the synergistic inhibition of ferroptosis in AD. By unravelling the complexities of AD and ferroptosis, the research not only addresses specific neurological challenges but also contributes to scientific knowledge, validating new disease mechanism, global health, and the well-being of dementia patients while inspiring researchers to seek this alternative axis for therapeutic avenues for neurodegenerative diseases.

Scientists have found that highly abundant naturally occurring plant-based polyphenols (PPs) like tannic acid found in twigs of trees like Chestnut

Potential Treatment Route For Alzheimer's Disease Found In Natural Polyphenol

Roorkee (The Hawk): September 21st, world Alzheimer's day, principally aimed at increasing awareness of dementia, its challenges and how to 'live-well' with the diagnosis. Reports show that people of South Asian Communities are less likely to get an early or 'timely' diagnosis, access to treatment or receive support when diagnosed. KINDURE, a social enterprise and brainchild of Dr Kavita D Mohan, consultant psychiatrist, UK, is envisioned at addressing the health issues, minimise stigma, increase awareness in South Asian (SA) Communities. Dr Kavita D Mohan, from Dehradun is passionate about mental health and mental wealth mastery. She is involved in various voluntary works, in UK and India. A seminar, hosted by High Commission of India, at a prestigious venue- Nehru Centre, London, on 21/9/2023. The attendees were from all walks of life- care-givers, health professionals or simply who wanted to learn more about the subject. Attendees appreciated the day gave excellent written and verbal feedbacks and encouragements to do more. The cherry on the cake was that many of the attendees, wish to stay connected, support and contribute.  The 'Guru Vandana' a tribute to start the day of learning, was performed by Mrs Gita Cox, a Xattriya dancer. Dr Kavita D Mohan, talked on the clinical &amp; technological aspects of dementias in the context SA community. Dr Mayuri Senapati, a consultant clinical psychologist engaged the audience with an overview of psychosocial and spiritual needs of patient with Dementia. Afifa Fatemi, masters in media, gave insight on the popular culture and dementia. Lived experience, is a concept of Learning from stories &amp; narratives from people who experience the illness or carers. Gita Cox, who has lived experience of dementia, recited a poetry written by a patient of Dr Kavita D Mohan and shared her experience of looking after her mother who suffers from early signs of dementia.

September 21st, world Alzheimer's day, principally aimed at increasing awareness of dementia, its challenges and how to 'live-well' with the diagnosis

Clinical & Technological Aspects Of  Dementia Discuss On World Alzheimer Day

Los Angeles [US]: Actor Chris Hemsworth is giving full attention to his health. In an interview with Men's Health, Hemsworth revealed that he has made major lifestyle changes after learning about his high risk for getting Alzheimer's disease, Fox News reported.
"Now, I'm incorporating more solitude into my life," Hemsworth, 40, shared. "I've always been pretty consistent with my exercise commitments, but lately I've really felt the importance of taking time for yourself without any outside voice or stimulation and making time for stillness," he added. The Thor star is now incorporating more time for "mindfulness work."
"I do a lot of meditation and breath work, mostly during sauna and ice bath routines," he added. "For me, my favorite mindfulness work comes from the immersion in physical actives that allow me to be fully present and force me out of me head and into my body, in particular surfing." In a conversation with longevity physician Dr. Peter Attia, the actor learned that he is eight to 10 times more likely than the average individual to develop Alzheimer's disease. "We've got every blood test one can get," Attia tells Hemsworth in the show. "And you've got two copies of APOE4. A set from your mom and a set from your dad." APOE4 is the gene that has the strongest correlation to the development of Alzheimer's disease; however, not much is known about it. At the time, Attia told the Australian actor, "It's my belief that if we take every step possible, we can reduce your risk to that of anyone else." Since then, Hemsworth has been making his health a top priority.
—ANI

Actor Chris Hemsworth is giving full attention to his health. In an interview with Men's Health, Hemsworth revealed that

The Hawk

Tag : Alzheimer

Target protein for diabetes can help to protect against Alzheimer's disease : Study

Preeti

Tag : Alzheimer

Target protein for diabetes can help to protect against Alzheimer's disease : Study

Preeti

More about Alzheimer